crossing96/oncoscreening huggingface dataset:
Identification of Hub Genes Associated with Progression and Prognosis of Bladder Cancer by Integrated Bioinformatics Analysis.	BACKGROUND: Bladder cancer (BLCA) is an extremely common carcinoma of the urinary system that has a high incidence of relapse. Although intensive studies have investigated its pathology in the past decades, there are significant knowledge gaps regarding the characterization of the molecular processes underlying the progression of disease and consequently its prognosis. The purpose of current research was to identify significant genes that could serve as prognostic and progression biomarkers. METHODS: Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA) were conducted to recognize differential co-expression genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore gene function. Moreover, protein-protein interactions (PPI) network, overall survival (OS) and disease-free survival (DFS) were used to identify survival-related hub genes. Additionally, associations between these gene's expression and clinical parameters were determined. Finally, the Human Protein Atlas (HPA) database and qRT-PCR were used to validate gene's expression. RESULTS: About 124 differential co-expression genes were identified. These genes were mainly enriched in muscle system process and muscle contraction (biological process, BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (cellular component, CC) and actin binding (molecular function, MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis. Furthermore, five survival-related hub genes (MYH11, ACTA2, CALD1, TPM1, MYLK) were identified via OS and DFS. In addition, these survival-related gene's expression was correlated with grade, stage and TNM stage. Finally, all survival-related hub genes were determined to be down-regulated in BLCA tissues by qRT-PCR and HPA databases. CONCLUSIONS: Our current study verified five new key genes in BLCA, which may participate in the prognosis and progression and serve as novel biomarkers of BLCA.	bladder
Global changes in bladder cancer mortality in the elderly.	BACKGROUND: Bladder cancer is the 14th most common cause of cancer deaths worldwide and has a mean age of diagnosis of 73 years. Elderly people have fewer curative treatment options for muscle invasive bladder cancer. The aim of this study is to investigate how bladder cancer mortality has changed over the past forty years in different world regions to assess discrepancies between elderly and younger patients with bladder cancer. METHODS: Bladder cancer mortality data were extracted from the World Health Organisation's GLOBOCAN database. Age-standardised mortality rates (ASMR) for bladder cancer were computed by year, sex, region and Human Development Index (HDI) using the world standard population. RESULTS: Overall ASMR in all available countries with data between 1986 and 2014 for men aged ≥ 75 has decreased from 101.2 to 89.9 per 100,000 (-11.2%). The decrease in ASMR for men < 75 has been 0.3-2.0 per 100,000 (-39.4%). In women aged ≥ 75 ASMR has decreased from 26.9 to 22.5 per 100,000 (-16.4%) and in women < 75 the ASMR has decreased from 0.76 to 0.56 per 100,000 (-26.4%). Correlation analysis showed a positive linear relationship between Human Development Index (HDI) and improvement in age-standardised mortality rate in all ages. Pearson's coefficient showed that correlation was strongest in the 60-74 age group (r = -0.61, p < 0.001) and weakest in those aged ≥ 75 (r = -0.39, p = 0.01). CONCLUSION: Bladder cancer mortality is not improving in the elderly at the same rate as the rest of the population. Particular focus should be applied in future research to enhance and expand treatment options for bladder cancer that are appropriate for elderly patients.	bladder
Current advances in the application of nanomedicine in bladder cancer.	Bladder cancer is the most common malignant tumor of the urinary system, however there are several shortcomings in current diagnostic and therapeutic measures. In terms of diagnosis, the diagnostic tools currently available are not sufficiently sensitive and specific, and imaging is poor, leading to misdiagnosis and missed diagnoses, which can delay treatment. In terms of treatment, current treatment options include surgery, chemotherapy, immunotherapy, gene therapy, and other emerging treatments, as well as combination therapies. However, the main reasons for poor efficacy and side effects during treatment are the lack of specificity and targeting, improper dose control of drugs and photosensitizers, damage to normal cells while attacking cancer cells, and difficulty in delivering siRNA to cancer cells. Nanomedicine is an emerging approach. Among the many nanotechnologies applied in the medical field, nanocarrier-assisted drug delivery systems have attracted extensive research interest due to their great translational value. Well-designed nanoparticles can deliver agents or drugs to specific cell types within target organs through active targeting or passive targeting (enhanced permeability and retention), which allows for imaging, diagnosis, as well as treatment of cancer. This paper reviews advances in the application of various nanocarriers and their advantages and drawbacks, with a focus on their use in the diagnosis and treatment of bladder cancer.	bladder
NUPR1 imparts oncogenic potential in bladder cancer.	BACKGROUND: NUPR1, or p8, is a small chromatin protein that plays a central role in the resistance to treatment and progression of cancer. Nevertheless, the molecular mechanism of NUPR1 in bladder cancer (BLCA) remains unclear. METHODS: We used online databases and immunohistochemistry (IHC) to explore the expression of NUPR1 in BLCA tissues and controls. Lentivirus-mediated small interfering ribonucleic acid (siRNA) was used to knockdown the expression of NUPR1 in two human BLCA cell lines. We used an in vivo experiment to investigate the effect of NUPR1 knockdown on the growth of BLCA. Moreover, an in silico analysis was conducted to assess the differential expression profile after NUPR1 interference. The CIBERSORT algorithm was utilized to evaluate the effects of tumor-infiltrating immune cells among BLCA patients. RESULTS: The expression of NUPR1 in BLCA tissues was significantly higher than in the control. NUPR1 expression was also positively correlated with the stage of BLCA. After lentivirus-mediated interference, the expression of NUPR1 was significantly down-regulated in BLCA cell lines. The cell cycle was blocked in G1 phase and the cell proportion of S phase was decreased in both two cell lines. Moreover, in vivo experiment revealed that the tumor growth of BLCA can be delayed by inhibiting the expression of NUPR1. Both in silico analysis and functional experiments revealed that NUPR1 was correlated with epithelial-mesenchymal transition (EMT). We also revealed that macrophages were the most related immune cells associated with the expression of NUPR1 in BLCA. CONCLUSIONS: This study suggests that NUPR1 plays a carcinogenic role in BLCA. NUPR1 lentivirus-mediated interference could interfere with cycle progression of the BLCA cell, resulting in cell cycle arrest in the G1-phase. The carcinogenic effect of NUPR1 in BLCA is likely achieved through EMT. NUPR1 is correlated with the M0-type macrophage markers CD68 and CD11b-integrin.	bladder
Oncologic and Safety Outcomes for Endoscopic Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An Updated Systematic Review and Meta-analysis.	We systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). Studies comparing oncologic and/or safety results for EM versus RNU in patients with UTUC were included in our review. Overall, 13 studies met the criteria, and five studies were included in a meta-analysis using adjusted hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). EM was associated similar OS (HR 1.27, 95% confidence interval [CI] 0.75-2.16), CSS (HR 1.37, 95% CI 0.99-1.91), and BRFS (HR 0.98, 95% CI 0.61-1.55) to RNU, while 28-85% of patients treated with EM experienced upper tract recurrence across the studies. EM required more interventions with a higher cumulative risk of complications and lower likelihood of renal preservation. In summary, EM for low-grade UTUC had comparable survival outcomes to RNU at the cost of higher local recurrence rates resulting in a need for long-term rigorous surveillance and repeated interventions. PATIENT SUMMARY: For selected cases of cancer in the upper urinary tract, surgical treatment via a telescope inserted through the urethra or the skin (endoscope) results in cancer control outcomes that are comparable to those after removal of the kidney and ureter. However, because of its higher rate of local recurrence, this approach requires repeated endoscopic treatment sessions. Patients should be well informed about these issues to help in shared decision-making.	bladder
A prospective descriptive 1-year study in France of all BCG therapy dispensations for non-muscle-invasive bladder cancer.	OBJECTIVES: To describe the clinico-pathological characteristics of non-muscle-invasive bladder cancer (NMIBC) treated in metropolitan France over 1 year when bacille Calmette-Guérin (BCG) was subject to a national quota, and to document, in the context of recurrent shortages of intravesical BCG for NMIBC, the real-life indications for adjuvant treatment. MATERIALS AND METHODS: Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology to propose a science-based quota solution for BCG using a clinical score. The ANSM then asked the distributor of the drug, MEDAC, to collect the scores for all patients for whom BCG was requested by healthcare institutions and to prioritize the requests for patients with the highest scores. Tumour stage, grade, size, number, time to recurrence, carcinoma in situ, age, accessibility of alternative treatments (total cystectomy, radio-chemotherapy, thermo-chemotherapy) and BCG treatment progress (initiation or maintenance) were documented for each intravesical BCG prescription. A descriptive analysis of the data collected during the quota year was performed. RESULTS: During the 1-year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were aged ≥70 years. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 prescriptions (50.9%), respectively. NMIBC treated with BCG maintenance therapy was more frequently high-risk NMIBC (91.7% vs 90.2%; P < 0.0001) than NMIBC for which induction therapy was requested. The number of cases of NMIBC leading to BCG adjuvant treatment was estimated at 12 704 cases/66 062 188 inhabitants over 1 year in metropolitan France. CONCLUSIONS: Our data suggest that the incidence of NMIBC at high risk of recurrence and progression is underestimated in reference epidemiological studies. These results should help to better define future care needs.	bladder
Bladder cancer tissue-derived exosomes suppress ferroptosis of T24 bladder cancer cells by transporting miR-217.	It has been reported that miR-217 can inhibit the oncogenic activity and progression of bladder cancer (BCa) cells, but it has not been explored whether miR-217 is involved in the regulation of ferroptosis. In the present study, RNA transfection, real-time PCR, flow cytometry, Western blotting assays, immunofluorescence and ELISA were performed to explore the effects and mechanisms of miR-217 in BCa tissue-derived exosomes. We found that extracellular fluid from bladder cancer tissue promoted the growth and miR-217 expression of T24 cells and inhibited ferroptosis. MiR-217 was confirmed to inhibit ferroptosis in bladder cancer cells by RNA interference and functional assays. By cell membrane fluorescence probe (CM-Dil) labeling, inhibiting exosome secretion by GW4689 and exosome extraction, we determined that BCa tissue-derived exosomes transport miR-217 into T24 cells. Culture of T24 cells with extracellular fluid after RNA interference showed that exosomes carrying miR-217 derived from BCa tissues inhibited ferroptosis of T24 cells. We conclude that bladder cancer tissue-derived exosomes inhibit ferroptosis of T24 bladder cancer cells by transporting miR-217. The results of our study provide a new insight into the progression of bladder cancer.	bladder
RFWD3 acts as a tumor promotor in the development and progression of bladder cancer.	BACKGROUND: Bladder cancer is one of the most commonly diagnosed malignancies of the urinary system with relatively poor prognosis and insufficient treatment strategies. RFWD3 is an E3 ligase whose function is rarely investigated in malignant tumors. METHODS: A tissue microarray was used for evaluating RFWD3 expression in clinical samples and its correlation with tumor characteristics and patients' prognosis. RFWD3 knockdown and overexpression cell models were constructed for conducting loss-of-function and gain-of-function assays. qPCR and western blotting were used for detecting mRNA and protein levels of RFWD3, respectively. MTT assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were carried out to demonstrate the change of cell phenotypes upon RFWD3 knockdown. RESULTS: RFWD3 expression was relatively higher in bladder cancer tissues than in normal tissues, which is correlated with higher N stage and poorer prognosis of patients. Knockdown of RFWD3 in bladder cancer cells significantly inhibited cell proliferation, colony formation, promote cell apoptosis and restrained cell migration. Overexpression of RFWD3 induced the opposite effects. CONCLUSIONS: It was illustrated that RFWD3 possesses excellent tumor-promoting ability in bladder cancer. Accordingly, RFWD3 may be a promising therapeutic target in the targeted therapy of bladder cancer, which is worth further research.	bladder
The prognostic impact of tumor necrosis in non-muscle invasive bladder cancer.	OBJECTIVE: We aimed to investigate the impact of tumor necrosis in non-muscle invasive bladder cancer on patients' recurrence and progression rates and survival outcomes. METHODS: This study was conducted retrospectively in a single tertiary center in Turkey. Medical records of patients who underwent transurethral resection of the bladder tumor between January 2016 and January 2021 were reviewed. Patients with pTa and pT1 non-muscle invasive bladder cancer who had undergone complete resection were included in our study. All pathological specimens were reevaluated for the presence of tumor necrosis. RESULTS: A total of 287 patients (244 males and 43 females) were included in our study. Of them, 33 (11.5%) patients had tumor necrosis. The rates of multiple and large tumors (>3 cm) were higher in patients with tumor necrosis (p=0.002 and p<0.001, respectively). Tumor necrosis was associated with higher rates of pT1 diseases (p<0.001), high-grade tumors (p<0.001), and the presence of lymphovascular invasion (p=0.007). The mean recurrence-free survival of patients with tumor necrosis was 42.3 (4.6) months, and the recurrence-free survival of patients without tumor necrosis was 43.5 (1.8) months (p=0.720). The mean progression-free survival of patients with tumor necrosis was 43.1 (4.6) months, and the progression-free survival of patients without tumor necrosis was 58.4 (0.9) months. In log-rank analysis, there was a statistically significant difference between patients with and without tumor necrosis in terms of progression-free survival (p<0.001). CONCLUSION: In this study, we demonstrated that patients with non-muscle invasive bladder cancer and tumor necrosis in pathological specimens have shorter progression-free survival and more adverse pathological features.	bladder
Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study.	IMPORTANCE: Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. OBJECTIVE: To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. DESIGN, SETTING, AND PARTICIPANTS: The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. EXPOSURES: Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. RESULTS: A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). CONCLUSIONS AND RELEVANCE: These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.	bladder
Novel synthetic lethality drug target in urothelial bladder cancer based on MTAP genomic loss.	BACKGROUND: When urothelial carcinoma of the bladder (UCB) presents or progresses to chemo-refractory metastatic disease, the search for new therapeutic targets is paramount. Targeting protein arginine methyltransferase 5 accumulation in tumors with methylthioadenosine phosphorylase (MTAP) genomic loss has been proposed as a new anti-tumor strategy. We evaluated the incidence of patients with MTAP loss and correlate to treatment-guiding targets and biomarkers. METHODS: Two thousand six hundred eighty-three cases of advanced UCB underwent hybrid-capture based comprehensive genomic profiling using the FDA-approved F1CDx assay to evaluate all classes of genomic alterations (GA) among 324 genes. Tumor mutational burden was determined on at least 0.8 Mbp of sequenced DNA and microsatellite instability was determined on at least 95 loci. RESULTS: 650 (24%) of UCB featured MTAP loss mutations (MTAP-). The gene and age distributions were similar in MTAP intact (MTAP+) and MTAP- UCB. MTAP- UCB contained higher GA/tumor frequency than MTAP+ UCB likely reflecting the frequent co-deletions of cyclin-dependent kinase inhibitor 2A/B. Of potential therapeutic targets, fibroblast growth factor receptor 3, and phosphatase and tensin homolog GA were more frequent in MTAP- UCB. In contrast, biomarkers of immunotherapy response, including higher frequencies of high tumor mutational burden and high programmed death-ligand 1 IHC staining, were observed in the MTAP+ UCB. CONCLUSIONS: When compared with MTAP+ UCB, MTAP- UCB differs in genomic signatures including an increase in potentially targetable alterations but a lower frequency of immunotherapy drug biomarkers. Thus, the genomic landscape in MTAP- UCB may play a role in the design of clinical trials incorporating combination treatment strategies when targeting protein arginine methyltransferase 5 in MTAP- tumors.	bladder
Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.	BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs. METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts. RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo . CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.	bladder